Category Archives: Drug discovery

Drug discovery

AstraZeneca neither confirms nor denies that it will ditch antibiotics research

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A computer image of a cluster of drug-resistant Mycobacterium tuberculosis.
{credit}US Centers for Disease Control and Prevention/ Melissa Brower{/credit}

The fight against antibiotic-resistant microbes would suffer a major blow if widely circulated rumours were confirmed that pharmaceutical giant AstraZeneca plans to disband its in-house antibiotic development. The company called the rumours “highly speculative” while not explicitly denying them.

On 23 October, drug-industry consultant David Shlaes wrote on his blog that AstraZeneca, a multinational behemoth headquartered in London, “has told its antibiotics researchers that they should make efforts to find other jobs in the near future”, and that in his opinion this heralds the end of in-house antibiotic development at the company. “As far as antibiotic discovery and development goes, this has to be the most disappointing news of the entire antibiotic era,” wrote Shlaes.

AstraZeneca would not directly address these claims when approached by Nature for comment. In its statement it said, in full:

The blog is highly speculative. We continue to be active in anti-infectives and have a strong pipeline of drugs in development. However, we have previously said on a number of occasions that as we focus on our core therapy areas (Oncology, CVMD [cardiovascular and metabolic diseases] and Respiratory, Inflammation and Autoimmune) we will continue to remain opportunity driven in infection and neuroscience, in particular exploring partnering opportunities to maximise the value of our pipeline and portfolio.

Research into antibiotics is notorious for its high cost and high failure rate. AstraZeneca has previously said that its main research focus would be on areas other than antibiotic development.

Public-health experts have been warning about a trend among large pharmaceutical companies to move away from antibiotics research — just as the World Health Organization and others have pointed to the rising threat of deadly multi-drug-resistant strains of bacteria such as Mycobacterium tuberculosis or Staphylococcus aureus (see ‘Antibiotic resistance: The last resort‘).

Scripps president resigns after faculty revolt

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The president of the Scripps Research Institute intends to leave his post, according to a statement from Richard Gephardt, the chair of the institute’s board of trustees. The announcement came in the wake of a faculty rebellion against the president, Michael Marletta, who had attempted to broker a deal in which the research lab, in La Jolla, California, would be acquired by the Los Angeles-based University of Southern California (USC) for US$600 million.

In the statement, posted on 21 July, Gephardt said that Marletta “has indicated his desire to leave” Scripps and that the board “is working with Dr Marletta on a possible transition plan”.

Scripps Research Institute president Michael Marletta resigned after clashing with faculty over a proposed merger.

Scripps Research Institute president Michael Marletta resigned after clashing with faculty over a proposed merger.{credit}Scripps Research Institute{/credit}

Scripps faculty members see Marletta’s departure as a victory. They had been angered by the terms of the USC deal, which was scrapped on 9 July, and by the fact that Marletta did not consult with faculty during his negotiations with USC. Faculty members told the Scripps board of trustees earlier this month that they had an almost unanimous consensus of no confidence in Marletta.

“I think we are more optimistic than we have been in many years, because we feel like we have some control over our own fate,” says Scripps biologist Jeanne Loring.

Loring said that at a meeting with a majority of Scripps faculty on 21 July, Gephardt indicated that the board had thought that Marletta was communicating with the faculty as he negotiated the USC deal. Gephardt also promised that faculty would involved in choosing Marletta’s successor.

Whoever replaces Marletta must find a way to close a projected $21-million budget gap this year left by the contraction of funding from the US National Institutes of Health (NIH) and by the virtual disappearance of support from pharmaceutical companies, who had provided major support for Scripps until 2011.

How Scripps solves its funding issue will be watched by other independent institutes, which have been hard hit by the contraction in NIH dollars. Scripps’ neighbour institutes have brought in hundreds of millions of dollars in philanthropy, and many involved see that as part of the solution for Scripps as well. But, Loring says, “the funding that other institutes have got from philanthropy is going to be a short-term solution, because even though it seems like an awful lot of money, they have to spend it, so they will eventually be facing the same issues.”

Follow Erika on Twitter: @Erika_Check.

 

Chimps from controversial lab move to retirement home

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Posted on behalf of Katia Moskvitch.

Juliussohappy_AF-300x199

Julius, 46, is one of 110 research chimps who are now permanently retired at a sanctuary in Louisiana.
Credit: Chimp Haven

Tosha, Sassy, Paula, Julius and their 106 friends will now be munching peppers and bananas without worries of being used to test new drugs. The chimpanzees, formerly used for biomedical research by the US National Institutes of Health (NIH) facility New Iberia Research Center (NIRC) in Louisiana, have now arrived at Chimp Haven, a federally funded sanctuary in Keithville, Louisiana.

“Our dreams have finally been realized for these amazing animals,” said Chimp Haven’s president Cathy Willis Spraetz in a statement.

The move comes two years after the NIH announced it would retire the NIRC’s 110 chimps, following an undercover video investigation by the Humane Society of the United States that exposed animal mistreatment at the facility (see ‘NIH retires research chimps at troubled facility‘).

Initially, the NIH had planned to send only ten of the animals to Chimp Haven and the rest to the Texas Biomedical Research Institute in San Antonio. The NIH changed its mind after the sanctuary embarked on an extensive campaign that resulted in making extra room at Chimp Haven to accommodate many more animals and raising money for their care.

Although experiments on chimps contributed to several medical breakthroughs, such as vaccines against hepatitis B and polio, recent scientific developments have created viable alternatives to primate research.

The retirement plan for the NIRC’s chimps was just the first step in scaling back the NIH’s primate research. In June 2013, the NIH announced it would retire to sanctuary nearly all of its research chimpanzees, about 310 of them, leaving only up to 50 for scientific experiments. NIH director Francis Collins said at the time that chimps, as humans’ closest living relatives in the animal kingdom, “deserve special respect”.

The decision followed a landmark report by the US Institute of Medicine published in December 2011, which outlined strict criteria for the use of chimps in biomedical and behavioural research.

 

 

 

 

WHO postpones decision on destruction of smallpox stocks — again

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The stalemate continues over the question of when to destroy the last stocks of the virus that causes smallpox, a killer disease that was eradicated in 1980. One of the World Health Organization’s (WHO) two advisory committees on smallpox supports the stocks’ destruction, and the other opposes it. Last weekend, health ministers of the WHO’s 194 member states again postponed a decision and decided to set up a third WHO smallpox advisory committee in a bid to broker a consensus.

The issue came up again on the agenda of the annual meeting of the World Health Assembly, the WHO’s top decision-making body, which was held in Geneva, Switzerland, from 19 to 24 May. It was last discussed at the 2011 assembly, which reaffirmed that the stocks of the variola virus should be destroyed but deferred to this year’s meeting discussion on any date of destruction.

A central question remains whether research of public-health importance is still needed on the virus, or whether the last stocks should be destroyed to eliminate the threat of an accidental release from the two labs where they are held — at the US Centers for Disease Control and Prevention in Atlanta, Georgia, and the Russian State Research Center of Virology and Biotechnology in Koltsovo, near Novosibirsk.

The final agenda of this year’s meeting, however,  asked ministers only to take note of a WHO update report to the assembly on progress on completing needed research. The WHO’s ‘advisory committee on variola virus research’ (ACVVR), which oversees and approves any research using the stocks, felt that live virus was no longer needed to develop diagnostics and vaccines, but was still needed to develop antiviral drugs. By contrast, its ‘advisory group of independent experts to review the smallpox research programme’ (AGIES) felt that there was no research justification for holding on to the stocks.

Although the ACVVR reached a consensus on antivirals, there was considerable debate about this among its members. Some argued, for example, that with two promising drugs — tecovirimat and brincidofovir — close to licensing, virus stocks were no longer needed. Others felt that the virus should be kept in case these drugs failed to get licensed, requiring the development of other compounds.

The AGIES considered the same issues but swung towards virus being no longer needed to develop antivirals — it also suggested that should a future need arise to develop new drugs, live virus could in any case be recreated from viral DNA. The ACVVR is often perceived as being more focused on research interests, and the AGIES on public-health aspects.

By the time the WHO assembly got to discussion of destruction of smallpox stocks, it was near the end of the last day of the meeting. It quickly became clear that there were sharply divided opinions and no consensus, according to Glenn Thomas, a WHO spokesman. The decision to setup a third expert group is intended to bring together a mix of scientists and public-health and other experts to review all the elements of the debate and take the issue forward, says Thomas.

For the moment, the precise terms of reference of the group, or its composition, have yet to be decided. The latter will be important, as the destruction of the variola stocks is also a political issue. The United State is strongly opposed to destruction of the virus stocks, largely because — like many other developed countries — it wants to pursue research that it believes might help to protect against a bioweapons attack by rogue states or terrorists, who may have access to undeclared stocks (see ‘WHO to decide fate of smallpox stocks‘).

Some scientists are also keen for smallpox research using live virus not to be stopped, but continued and expanded. Two members of the ACVVR, Clarissa Damaso, of the Federal University of Rio de Janeiro in Brazil, and Grant McFadden, of the University of Florida in Gainesville, have argued, for example, that the WHO’s restricting of smallpox research to tightly circumscribed public-health applications has limited fundamental research that could advance public health. In an opinion piece published 1 May in the journal PLoS Pathogens, along with Inger Damon, head of the poxvirus and rabies branch of the Centers for Disease Control and Prevention in Atlanta, Georgia, they argue that: “the research agenda with live variola virus is not yet finished and that significant gaps still remain”.

But the majority of the health ministers of the WHO member states — including those of many poorer countries, who view the risks of an accidental release as outweighing any research benefits — want the stocks of virus destroyed at some point. The question for the WHO assembly is, as always, when? But yet again, it has kicked that can down the road.

NIH to require sex-reporting in preclinical studies

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The US National Institutes of Health (NIH) will require grant applicants to report the sex of animals and cells used in preclinical studies, officials said today.

The shift could help to reveal differences in the ways that diseases affect males and females. Depression, for instance, more often causes anger in males and hopelessness in females; failing to account for this type of variation can skew research results. It can also be dangerous — last January, the US Food and Drug Administration halved the recommended dose of the sleep aid Ambien for women. Although the drug has been available for 22 years, researchers only recently discovered that women who take Ambien are at increased risk of accident. 

The NIH has long recognized animal sex bias as a problem, says Janine Clayton, director of the agency’s Office of Research on Women’s Health (ORWH), who announced the agency’s new policy in a Nature commentary with NIH director Francis Collins.

A 1993 law requires that NIH-funded clinical trials include women, with few exceptions, and the numbers of participants recruited to such trials appear to have evened out over time. “If you look at NIH clinical research last year, over 50% of participants were women,” says Clayton. “It’s in the preclinical space where we haven’t seen a corresponding revolution.”

Much of this, she says, is due to a belief that the oestrus cycle affects the female animals’ physiology and throws off results; as a result, researchers tend to prefer male animals, though recent meta-analysis studies of literature have shown that this is not the case. (Some studies use female animals because they can be housed in groups, whereas male animals tend to fight unless given their own cages.)

Under the new NIH policy, which will begin to take effect in October of this year, grant applicants will have to describe how they plan to balance the sexes for cells and animals used in their studies. Clayton says that the NIH rules will not be so prescriptive as to require equal numbers of males and females, but both sexes must be represented. “This is more than a numbers game,” she says.

The NIH will monitor whether its grantees are complying with these plans “so we get pinged if there’s a problem,” says Clayton. There will be exceptions — research on reproductive organs, for example — but they will be few and far between.

In recent years, researchers have come to recognize the importance of sex differences in animal work, and many are actively including both sexes and reporting them in the methods of their papers, says Sherril Green, a comparative pathologist at Stanford University in California. She adds that pharmaceutical companies are also separating animals by sex early in the drug development process so as to avoid costly missteps such as the case with Ambien, which may have been avoided with more testing in women.

Yet the problem is bigger than just sex bias: factors such as age and genetic background can all greatly influence how an animal responds to a treatment. Brad Bolon, a veterinary pathologist at Ohio State University in Columbus, thinks the new NIH rules ignore the real problem. “By drawing so much attention to matter of sex, it avoids the whole crux of the issue,” which is too little transparency on the details of experimental design as a whole, he says.

Bolon also worries about added costs that may result from the new rules. To get enough statistical power to draw conclusions about each sex, researchers may need to double the number of animals used in the study. “Arbitrarily saying that research must be done in both sexes, especially early on, is going to take money out of testing truly novel hypotheses,” he says.

In recognition of such concerns, in 2013 the ORWH began offering funding supplements to grantees to allow them to add the appropriate number of animals to their studies. But Clayton says that this programme will probably be eliminated because investigators must now begin accounting for sex difference in their experiments from the very beginning.

Bolon says that a more direct way to persuade scientists to use both sexes in their research would be for journals to require reporting of certain variables in their methods sections. Many journals already have such guidelines, and Clayton says that NIH plans to work with journals so that sex reporting becomes the norm.

Editor’s note: a previous version of this story incorrectly referred to the “gender” of lab animals and cells rather than their “sex”.

UK politicians wade into pharma mega-deal

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Pharmaceutical giant Pfizer has attempted to reassure UK politicians over its attempts to buy AstraZeneca, as political parties traded blows over the potential merger.

AstraZeneca today rejected an improved offer of approximately £50 (US$84) per AstraZeneca share from New York-based Pfizer, which would have valued the London-based company at around £63 billion ($106 billion).

As well as releasing this new bid, Pfizer today took the unusual move of sending a public letter to Prime Minister David Cameron, after a number of commentators expressed fears that a merger could devastate the UK research ecosystem if the resulting company slashed research and development (R&D). In 2011 Pfizer shocked many observers in the United Kingdom when it closed the Sandwich research park as part of global cuts to research.

“We recognize that our approach [to buy AstraZeneca] may create uncertainty for the UK Government and scientific community,” says the letter. It also commits Pfizer to setting its corporate and tax headquarters in the United Kingdom, completing AstraZeneca’s planned research site in Cambridge and employing at least 20% of the merged company’s R&D work force in the country.

On BBC radio this morning the government’s science minister sparred with his opposition number over the merger.

“We have been having very tough conversations with Pfizer and have made it clear to them that the British government attaches great importance to the R&D activities happening here in Britain and also manufacturing,” said science minister David Willetts. He added the government would expect Pfizer to commit to R&D and manufacturing in the United Kingdom if there were a merger but that this would ultimately be a decision for the AstraZeneca stakeholders.

But his counterpart in the opposition, shadow science minister Chuka Umunna, said that Pfizer has a “very poor” record on previous purchases, which had led to “deep cuts” in research facilities, and that the government was not doing enough to protect UK research.

New cholesterol drugs make strides in clinical trials

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The excitement around PCSK9 — a promising protein target for cholesterol-lowering therapies — seems to be justified. This week, at the American College of Cardiology’s annual meeting in Washington DC, several pharmaceutical companies presented data from advanced clinical trials showing that monoclonal antibodies that target and degrade PCSK9 are effective at treating patients with high cholesterol, especially when combined with statins such as Lipitor.

PCSK9, which circulates in the blood, prevents the liver from importing and processing low-density lipoprotein (LDL), or ‘bad’ cholesterol. People with genetic mutations that lower levels of PCSK9 in the blood also have lower cholesterol levels. (A 2013 feature story in Nature details how PCSK9 was discovered through the Human Genome Project.)

In one of five advanced-stage clinical trials it presented this week, Amgen, based in Thousand Oaks, California, showed that its new drug, evolocumab, lowered cholesterol by 57%, on average, in 901 patients who took the drug for a year. The company is in the process of enrolling more than 30,000 people in further clinical trials.

Evolocumab has two close competitors.  One is alirocumab, made by Sanofi, based in Bridgewater, New Jersey, and Regeneron, based in Tarrytown, New York. Alirocumab lowered cholesterol by nearly 50% compared to a placebo, and by 75% when combined with a statin. Finally, New York City-based Pfizer showed that its drug bococizumab lowers cholesterol by up to 67% when combined with a statin.

Jay Edelberg, who heads PCSK9 development at Sanofi, says that monoclonal antibody treatments could be especially useful for people who cannot take statin drugs or who have a genetic predisposition to high cholesterol.

All four companies now have larger trials underway, in which they will continue testing for adverse effects and determine whether the lowered cholesterol actually decreases a patient’s risk of heart disease. If all goes well, Amgen plans to file for regulatory approval for evolocumab later this year, and Sanofi and Regeneron plan to file in 2015.

 

 

New revelations on controversial stem-cell foundation in Italy

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Following the leak last month of a treatment protocol for a controversial stem-cell therapy earmarked for a clinical trial to be sponsored by the Italian government, further leaks from police investigations and other revelations are emerging daily about the activities of the trial’s sponsor, the Stamina Foundation.

The foundation has treated scores of seriously ill patients with the therapy since 2007, and its president Davide Vannoni has whipped up a frenzy of support among the families of dying patients to whom he claims to offer a cure. He has also so far managed to maintain political support.

Now, however, Stamina’s case appears to be unravelling.

On 12 December the newspaper La Stampa published an article describing, based on police witness accounts, how the Stamina Foundation’s roots lay in a call centre run by Vannoni, called Cognition Turin. After experiencing a partial facial paralysis in 2004, he went to Russia seeking a stem cell‒based treatment. He brought back with him two Ukrainian scientists and set up a small lab for them in Cognition’s basement, described by a police witness who had worked there as tiny and dark, with no ventilation. The lab was equipped with a couple of fridges and a few microscopes on a shelf, said the witness. Patients began to arrive from all over Italy.

In its early years, Stamina enjoyed political protection in the Piedmont region, which agreed to provide it with a grant of half a million euros to develop its stem-cell activities. But the region dropped the plan at the last minute after police in Turin began investigating possible fraud in relation to the proposed Piedmont grant. That investigation led to Vannoni being indicted for attempted fraud last month.

Patients were charged tens of thousands of euros for treatment, which consisted of extracting stem cells from their bone marrow, manipulating them in vitro (ostensibly to turn them into neurons) and delivering them back into the blood stream or spinal cords of the same patients.

Police are investigating the fate of 68 patients, or their families,  who claim they were damaged by Stamina treatment.

On 9 January, La Stampa published an interview with Milena Mattavelli, whose husband died within eleven days of his first Stamina injection, though doctors had expected him to live with his incurable disease, multiple system atrophy, for several more years.  Mattavelli said she paid Stamina €50,000 in cash and got no receipt.

In another revelation, the father of a young child treated by Stamina told the police investigators that he also paid €50,000 and had been told by Stamina to transfer the money using a description ‘contributions, donations and offerings’ because the procedure was illegal in Italy. His daughter’s condition, not named in the newspaper article, did not improve.

Nicola De Matteis, whose daughter was born with encephalopathy, ran out of money after several treatments and was told by Stamina’s physician Marino Andolina to make his wife earn it through prostitution, according to an article in La Stampa on 13 January. Andolina did not respond to an email requesting comment.

Meanwhile the University of Udine, where Vannoni had been an assistant professor in psychology, has revoked his teaching contract, saying his “role in the university is no longer compatible with his other activities as president of the Stamina Foundation.” Vannoni says he was leaving anyway to join an online university.

And more top scientists have distanced themselves from diabetes expert Camillo Ricordi from the University of Miami in Florida, who has frequently voiced support for Stamina, and who holds a potentially influential position in Italy as the new president of RiMED, a translational-medicine institute being established in Sicily whose mandate includes development of cellular therapies. Ricordi had also offered to test Stamina cells in his Miami laboratories, although on 13 January he said he would “postpone” the offer.

Immunologist Alberto Mantovani, scientific director of the Clininal Institute Humanitas IRCCS in Milan, and cell biologist Tullio Pozzan from the University of Padua have resigned from RiMED’s scientific board, citing concern that Ricordi has declined to condemn Stamina.  They join cancer researcher Carlo Croce from the Ohio State University in Columbus, who resigned for the same reason at the end of December. The scientific board is now left with just three (non-Italian) members.

Lack of transparency casts doubt on Tamiflu’s efficacy, say UK politicians

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Doctors, researchers and patients are being undermined by a practice of “routinely and legally” withholding the results of clinical trials from them, a group of British politicians says.

In a report released today on the United Kingdom’s stockpiling of the drug Tamiflu, used to treat influenza during a pandemic, the Committee of Public Accounts of the House of Commons has weighed in to the debate over access to clinical-trial data. The United Kingdom has spent £424 million (US$697 million) in recent years stockpiling Tamiflu, but had to write off £74 million of this, as it was not clear the medicine had been stored correctly.

A vocal group of medical researchers has questioned the evidence base for Tamiflu, in part because they say that many details of trials of the drug have not been released by its manufacturer, Roche, which is headquartered in Basel, Switzerland. Their campaign has been spearheaded by the Cochrane Collaboration, which is a group of medical researchers, and the British Medical Journal.

Richard Bacon, a member of the committee, said in a statement that the committee was “disturbed by claims that regulators do not have access to all the available information”. He also said that a “lack of transparency of clinical-trial information on this drug to the wider research community” is hindering proper assessment of Tamiflu’s efficacy.

“The ability of doctors, researchers and patients to make informed decisions about treatments is being undermined,” says Bacon.

The report from comes just days after an industry scheme to share data from clinical trials came into force, backed by the European Federation of Pharmaceutical Industries and Associations (EFPIA) and the US Pharmaceutical Research and Manufacturers of America (PhRMA). The European Medicines Agency (EMA), the regulator for drugs in the European Union, is also pushing forward with plans to make more clinical-trial data available.

However, the new report says these moves are inadequate, as they do not address access to data from all trials, and, in particular, they do not apply to those from previous years.

In its response to the report, Roche said that its own policies on data sharing go beyond the EFPIA and PhRMA guidelines.

“We support the call for greater transparency in access to clinical-trial results. This is why we expanded our policy last year to provide enhanced access to data from our clinical trials,” read the statement.

The company says that it has already sent the Cochrane Collaboration all 77 of the studies it sponsored on Tamiflu, in line with its policy, which came into force last year.

On the other side of the arguments, Ben Goldacre, the co-founder of the AllTrials campaign for greater openness of clinical-trial data, called the report “a complete vindication” of the campaign.

“Industry has claimed it is on the verge of delivering transparency for over two decades,” he said in a statement. “While obfuscating and delaying, ever more results have been withheld.”

Patient’s suicide forces belated university investigation

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Posted on behalf of David Cyranoski.

In May 2004 Daniel Markingson, a patient with schizophrenia in an anti-psychotic drug trial at the University of Minnesota in Minneapolis, “stabbed himself to death in the bathtub with a box cutter, ripping open his abdomen and nearly decapitating himself,” as a magazine article would report six years later.

Controversy has rumbled since the story broke in May 2008. Should Markingson have been in the trial in the first place? Should he have been removed from it earlier? Were those running the trial negligent and, if so, does the university share responsibility?

The university has consistently denied wrongdoing. Critics, mainly bioethicists, have maintained that there are many unresolved issues. On 5 December, the university faculty senate agreed that there was a need for investigation into the way the university handles clinical research — but the ambiguous wording of its official statement has started another round of debate about how it will proceed.

The study, begun in March 2002 and sponsored by AstraZeneca, compared the tolerability and efficacy of three antipsychotic drugs that were already on the market. Stephen Olson, a psychiatry professor at the university, enrolled Markingson, his patient. Markingson’s condition deteriorated until his suicide.

Markingson’s mother, Mary Weiss, who had been trying to remove her son from the study for months, sued the university, Olson, the drug company and other parties. The court dismissed the various claims raised on legal grounds (“statutory immunity”) except for testimony that Olson failed to monitor Markingson’s compliance with the drug protocol and withheld information on risks and benefits of other treatments. This led him “to enter a drug study in which he was inadequately monitored, untreated, with this lack of treatment causing his psychosis to persist, thus causing his death by ritualistic, psychotic, suicide”.

In April 2008, Weiss and Olson settled out of court for US$75,000. University administrators have themselves called this a “nominal” fee, and Weiss told Mother Jones magazine in the 2010 article that it would not cover her own legal expenses. She also said that she agreed to a settlement only after the university threatened to sue her for court fees — a highly unusual request in the US legal system.

The university administration has since insisted that the case was closed, pointing to the court ruling and to other “examinations”, such as those by the US Food and Drug Administration and the Minnesota Board of Medical Practice.

Bioethicists, however, continue to argue that, legal considerations aside, the university should establish responsibility, particularly about whether Markingson had been coerced into entering the trial and whether doctors missed warning signs. They point to Olson’s conflict of interest in enrolling his own patient in a study by which he stood to gain financially, and the fact that Olson had testified that Markingson “was mentally ill and lacked the capacity to make decisions regarding his medical treatment” a week before getting his informed consent to put him in the trial.

On 14 November, a letter to the Faculty Consultative Committee accompanied by 175 signatures of bioethicists, psychiatrists and legal experts, argued that each of the reviews that the university used to defend itself was either flawed or misinterpreted into suggesting that there was no wrongdoing. The letter called for an independent investigation.

The faculty senate resolution passed on 5 December calls for just that: “an independent and transparent examination”. The resolution says that “previous investigations did not address the broader question of whether the university’s procedures, practices and policies governing clinical research on human subjects, some of them changed since the Markingson case, reflect both best practices in clinical research on human subjects and the faculties high ambitions for ethical behavior”. The resolution passed 67 to 23.

Carl Elliott, a bioethicist at the university who has been pushing in vain for a re-investigation for years, was happily surprised to see member after member speaking in support of the measure at the senate hearing. He was also surprised to see Olson, who had generally shied away from making public statements about the case, step up to the microphone to defend himself with what Elliott considers a questionable comparison. Olson said: “Cancer patients die in cancer studies all the time, and it’s not a surprise that people with mental illness will die in a trial of mental illness.”

But will this new investigation put the matter to rest? The resolution specified an investigation of “current” practices and makes no explicit reference to re-opening the Markingson case, although it mentions it as the trigger for its investigation and it includes a clause noting the special demands for “oversight of clinical research involving adult participants with diminished functional abilities” — a clear reference to Markingson.

On 10 December, university president Eric Kaler told the Minnesota Daily, a student-run newspaper, that he is “willing to take the advice of the Senate and the panel”, with the goal of airing “out clearly and very publicly what we do and have a panel of external experts validate that and be sure we are doing this absolutely as well as can be done”. But, he added, it will not examine the Markingson case: “It’s not a review of the Markingson case; it’s a review of what we are doing now and what we’re going to do moving forward.”

The next day, on 11 December, Trudo Lemmens, a professor of health law and policy at the University of Toronto in Canada, and five of the other authors behind the petition, wrote to Kaler to tell him that their concerns would be met only if “the investigation covers problems in the Markingson case and examines whether other similar cases exist”.

Whether the Markingson case gets the thorough look Lemmens and others hope for might hinge on whether the committee is truly independent.